Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGB6NU0)

DOT Name Cullin-associated NEDD8-dissociated protein 1 (CAND1)
Synonyms Cullin-associated and neddylation-dissociated protein 1; TBP-interacting protein of 120 kDa A; TBP-interacting protein 120A; p120 CAND1
Gene Name CAND1
Related Disease
Lung cancer ( )
Lung carcinoma ( )
Non-small-cell lung cancer ( )
Pituitary gland disorder ( )
Renal cell carcinoma ( )
X-linked Emery-Dreifuss muscular dystrophy ( )
Neoplasm ( )
Adenocarcinoma ( )
Advanced cancer ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Hepatocellular carcinoma ( )
Liver cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
UniProt ID
CAND1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1U6G; 4A0C; 7Z8R; 7Z8T; 7Z8V; 7ZBW; 7ZBZ; 8CDJ; 8CDK; 8H3Q; 8OR0; 8OR2; 8OR3; 8OR4
Pfam ID
PF13513 ; PF08623
Sequence
MASASYHISNLLEKMTSSDKDFRFMATNDLMTELQKDSIKLDDDSERKVVKMILKLLEDK
NGEVQNLAVKCLGPLVSKVKEYQVETIVDTLCTNMLSDKEQLRDISSIGLKTVIGELPPA
SSGSALAANVCKKITGRLTSAIAKQEDVSVQLEALDIMADMLSRQGGLLVNFHPSILTCL
LPQLTSPRLAVRKRTIIALGHLVMSCGNIVFVDLIEHLLSELSKNDSMSTTRTYIQCIAA
ISRQAGHRIGEYLEKIIPLVVKFCNVDDDELREYCIQAFESFVRRCPKEVYPHVSTIINI
CLKYLTYDPNYNYDDEDEDENAMDADGGDDDDQGSDDEYSDDDDMSWKVRRAAAKCLDAV
VSTRHEMLPEFYKTVSPALISRFKEREENVKADVFHAYLSLLKQTRPVQSWLCDPDAMEQ
GETPLTMLQSQVPNIVKALHKQMKEKSVKTRQCCFNMLTELVNVLPGALTQHIPVLVPGI
IFSLNDKSSSSNLKIDALSCLYVILCNHSPQVFHPHVQALVPPVVACVGDPFYKITSEAL
LVTQQLVKVIRPLDQPSSFDATPYIKDLFTCTIKRLKAADIDQEVKERAISCMGQIICNL
GDNLGSDLPNTLQIFLERLKNEITRLTTVKALTLIAGSPLKIDLRPVLGEGVPILASFLR
KNQRALKLGTLSALDILIKNYSDSLTAAMIDAVLDELPPLISESDMHVSQMAISFLTTLA
KVYPSSLSKISGSILNELIGLVRSPLLQGGALSAMLDFFQALVVTGTNNLGYMDLLRMLT
GPVYSQSTALTHKQSYYSIAKCVAALTRACPKEGPAVVGQFIQDVKNSRSTDSIRLLALL
SLGEVGHHIDLSGQLELKSVILEAFSSPSEEVKSAASYALGSISVGNLPEYLPFVLQEIT
SQPKRQYLLLHSLKEIISSASVVGLKPYVENIWALLLKHCECAEEGTRNVVAECLGKLTL
IDPETLLPRLKGYLISGSSYARSSVVTAVKFTISDHPQPIDPLLKNCIGDFLKTLEDPDL
NVRRVALVTFNSAAHNKPSLIRDLLDTVLPHLYNETKVRKELIREVEMGPFKHTVDDGLD
IRKAAFECMYTLLDSCLDRLDIFEFLNHVEDGLKDHYDIKMLTFLMLVRLSTLCPSAVLQ
RLDRLVEPLRATCTTKVKANSVKQEFEKQDELKRSAMRAVAALLTIPEAEKSPLMSEFQS
QISSNPELAAIFESIQKDSSSTNLESMDTS
Function
Key assembly factor of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complexes that promotes the exchange of the substrate-recognition F-box subunit in SCF complexes, thereby playing a key role in the cellular repertoire of SCF complexes. Acts as a F-box protein exchange factor. The exchange activity of CAND1 is coupled with cycles of neddylation conjugation: in the deneddylated state, cullin-binding CAND1 binds CUL1-RBX1, increasing dissociation of the SCF complex and promoting exchange of the F-box protein. Probably plays a similar role in other cullin-RING E3 ubiquitin ligase complexes.
Reactome Pathway
Neddylation (R-HSA-8951664 )
Iron uptake and transport (R-HSA-917937 )
Neutrophil degranulation (R-HSA-6798695 )

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Lung cancer DISCM4YA Strong Biomarker [1]
Lung carcinoma DISTR26C Strong Biomarker [1]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [1]
Pituitary gland disorder DIS7XB48 Strong Biomarker [2]
Renal cell carcinoma DISQZ2X8 Strong Biomarker [3]
X-linked Emery-Dreifuss muscular dystrophy DISDPMZ3 Strong Genetic Variation [4]
Neoplasm DISZKGEW Disputed Biomarker [5]
Adenocarcinoma DIS3IHTY Limited Altered Expression [6]
Advanced cancer DISAT1Z9 Limited Biomarker [1]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Limited Biomarker [7]
Hepatocellular carcinoma DIS0J828 Limited Biomarker [7]
Liver cancer DISDE4BI Limited Biomarker [7]
Prostate cancer DISF190Y Limited Biomarker [6]
Prostate carcinoma DISMJPLE Limited Biomarker [6]
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⏷ Show the Full List of 14 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Cullin-associated NEDD8-dissociated protein 1 (CAND1). [8]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Cullin-associated NEDD8-dissociated protein 1 (CAND1). [9]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Cullin-associated NEDD8-dissociated protein 1 (CAND1). [10]
Diethylstilbestrol DMN3UXQ Approved Diethylstilbestrol decreases the expression of Cullin-associated NEDD8-dissociated protein 1 (CAND1). [11]
Piroxicam DMTK234 Approved Piroxicam increases the expression of Cullin-associated NEDD8-dissociated protein 1 (CAND1). [12]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Cullin-associated NEDD8-dissociated protein 1 (CAND1). [13]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate decreases the expression of Cullin-associated NEDD8-dissociated protein 1 (CAND1). [14]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the mutagenesis of Cullin-associated NEDD8-dissociated protein 1 (CAND1). [15]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the expression of Cullin-associated NEDD8-dissociated protein 1 (CAND1). [14]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Cullin-associated NEDD8-dissociated protein 1 (CAND1). [16]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Cullin-associated NEDD8-dissociated protein 1 (CAND1). [17]
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⏷ Show the Full List of 11 Drug(s)

References

1 miR-33a inhibits cell proliferation and invasion by targeting CAND1 in lung cancer.Clin Transl Oncol. 2018 Apr;20(4):457-466. doi: 10.1007/s12094-017-1730-2. Epub 2017 Sep 4.
2 Cullin-associated NEDD8-dissociated protein 1, a novel interactor of rabphilin-3A, deubiquitylates rabphilin-3A and regulates arginine vasopressin secretion in PC12 cells.Endocr J. 2018 Mar 28;65(3):325-334. doi: 10.1507/endocrj.EJ17-0399. Epub 2018 Jan 23.
3 New Insights Into the Mechanism of COP9 Signalosome-Cullin-RING Ubiquitin-Ligase Pathway Deregulation in Urological Cancers.Int Rev Cell Mol Biol. 2016;323:181-229. doi: 10.1016/bs.ircmb.2015.12.007. Epub 2016 Feb 16.
4 Induced expression, localization, and chromosome mapping of a gene for the TBP-interacting protein 120A.Biochem Biophys Res Commun. 1999 Dec 9;266(1):123-8. doi: 10.1006/bbrc.1999.1773.
5 Disclosing the Interaction of Carbonic Anhydrase IX with Cullin-Associated NEDD8-Dissociated Protein 1 by Molecular Modeling and Integrated Binding Measurements.ACS Chem Biol. 2017 Jun 16;12(6):1460-1465. doi: 10.1021/acschembio.7b00055. Epub 2017 Apr 19.
6 CAND1 promotes PLK4-mediated centriole overduplication and is frequently disrupted in prostate cancer.Neoplasia. 2012 Sep;14(9):799-806. doi: 10.1593/neo.12580.
7 Targeting CAND1 promotes caspase-8/RIP1-dependent apoptosis in liver cancer cells.Am J Transl Res. 2018 May 15;10(5):1357-1372. eCollection 2018.
8 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
9 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
10 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
11 Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
12 Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
13 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
14 Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
15 Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
16 Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
17 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.